There is no dearth of drugs that can kill cancer cells. The challenge is achieving specificity, i.e., killing the cancer cells while sparing the normal cells. There are three basic strategies now used to accomplish this specificity. One (selective toxicity) employs drugs that have more potent growth-inhibitory effects on tumor cells than on normal cells (1, 2) This strategy underlies the success of conventional chemotherapeutic agents as well as those of newer targeted therapies such as imatinib. The second strategy (delivery) employs agents such as antibodies or genes that specifically react with tumor cells or are predominantly expressed within tumor cells, respectively (3, 4). The third strategy (angiogenic) exploits abnormal aspects of tumor vasculature with agents such as Avastin (5, 6) or drugs incorporated into liposomes (7). Liposomes are relatively large particles that can penetrate through the fenestrated endothelium present in tumors and a few other organs (8, 9). Once they gain access to tumors, they persist and eventually release their contents and raise local drug concentrations through the enhanced permeabilization and retention (EPR) effect (10). Though each of these strategies has proven merit, the therapeutic results achieved are usually less than desired. The problems arise, in part, because the achieved specificity with any one of them is imperfect, limiting the amount of drug that can be safely administered without causing systemic toxicity.
There is a continuing need in the art to develop treatments for cancers that are more effective and less toxic.